The objective of this proposal is to identify new dominant gene defects in thyroid tumors, and to clarify the role of some of the mutations already discovered on the clinical behavior of thyroid neoplasms. The specific aims are to: 1) Determine the prognostic value of ras mutations in thyroid neoplasms: the hypothesis that point mutations and/or gene amplification of ras may predispose follicular or papillary carcinomas to undergo further transformation to a more aggressive phenotype will be tested; 2) Identify chromosomal locl affected by gene amplification in thyroid neoplasms; 3) Identify rapid turnover mRNAs overexpressed in human thyroid tumors; 4) Identify transforming cDNAs from human thyroid cancers by using a modified expression cloning strategy to isolate growth-promoting genes from thyroid cancer specimens.